Vasorelaxant and Antihypertensive Effects of Neferine in Rats: An In Vitro and In Vivo Study

Planta Medica ◽  
2020 ◽  
Vol 86 (07) ◽  
pp. 496-504 ◽  
Author(s):  
Piyawadee Wicha ◽  
Amnart Onsa-ard ◽  
Waraluck Chaichompoo ◽  
Apichart Suksamrarn ◽  
Chainarong Tocharus
Keyword(s):  
Nitric Oxide ◽  
Thoracic Aorta ◽  
Antihypertensive Effect ◽  
Soluble Guanylyl Cyclase ◽  
K Channel ◽  
Channel Blockers ◽  
Organ Bath ◽  
Hypertensive Rats

AbstractThe present study was performed to examine the antihypertensive effect of neferine in hypertensive rats and its relaxant mechanisms in isolated rat thoracic aorta. The antihypertensive effect was evaluated by tail-cuff methods on NG-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg BW) 4-week hypertensive-induced hypertensive rats. The vasorelaxant effect and its mechanisms were studied by the organ bath technique in the thoracic aorta isolated from normotensive rats. The results indicated that the treatment of neferine (1 mg/kg and 10 mg/kg) markedly decreased the systolic blood pressure (SBP) when compared with the hypertension group (137.75 ± 10.14 mmHg and 132.23 ± 9.5 mmHg, respectively, p < 0.001), without affecting the heart rate. Moreover, neferine (10−12 − 10−4 M) exhibited concentration-dependent vasorelaxation in endothelium-intact rings (Emax values = 98.95 ± 0.66% and pD2 = 7.93 ± 0.28) and endothelium-denuded rings (Emax values = 90.61 ± 1.91% and pD2 = 6.85 ± 0.36). The effects of neferine were reduced by pre-incubation with L-NAME and 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) but not with pre-incubation with indomethacin and K+channel blockers. Neferine attenuated the contractions induced by phenylephrine and caffeine in a Ca2+-free solution and also inhibited in CaCl2- and phenylephrine-induced contracted rings. Our study suggests that neferine exhibited hypertensive potential, induced vasorelaxation through the endothelium nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway and involved the modulation of Ca2+ influx through Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum.

Antihypertensive effects of fargesin in vitro and in vivo via attenuating oxidative stress and promoting nitric oxide release

2016 ◽  
Vol 94 (8) ◽  
pp. 900-906 ◽  
Author(s):  
Sha Sha ◽  
Dandan Xu ◽  
Yanwei Wang ◽  
Weifang Zhao ◽  
Xiaoni Li
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Antihypertensive Effect ◽  
Experimental Period ◽  
Biological Information ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Antioxidant Defence System

Fargesin, a bioactive neolignan isolated from magnolia plants, is widely used in the treatment of managing rhinitis, inflammation, histamine, sinusitis, and headache. To provide more biological information about fargesin, we investigated the effects of fargesin on rat aortic rings and 2-kidney, 1-clip (2K1C) hypertensive rats. In vitro, fargesin caused concentration-dependent vasorelaxation in rat isolated aortic rings induced by KCl and norepinephrine. The effect was weakened by endothelium denudation and nitric oxide (NO) synthesis inhibition. In vivo, the evolution of systolic blood pressure (SBP) was followed by weekly measurements. Angiotensin II (Ang II) and endothelin (ET) levels, NO and nitric oxide synthase (NOS), and plasma and liver oxidative stress markers were determined at the end of the experimental period. After 5 weeks of fargesin treatment, we found that fargesin treatment reduced SBP, cardiac hypertrophy, and Ang II and ET levels of hypertensive rats. Increased NOS activity and NO level were observed in fargesin-treated rats. Normalisation of plasma MDA concentrations and improvement of the antioxidant defence system in plasma and liver accompanied the antihypertensive effect of fargesin. Taken together, these results provided substantial evidences that fargesin has antihypertensive effect in 2K1C hypertensive rats via inhibiting oxidative stress and promoting NO release.

scholarly journals Heme proteins mediate the conversion of nitrite to nitric oxide in the vascular wall

2008 ◽  
Vol 295 (2) ◽  
pp. H499-H508 ◽  
Author(s):  
Wael F. Alzawahra ◽  
M. A. Hassan Talukder ◽  
Xiaoping Liu ◽  
Alexandre Samouilov ◽  
Jay L. Zweier
Keyword(s):  
Nitric Oxide ◽  
Heme Proteins ◽  
Soluble Guanylyl Cyclase ◽  
Vascular Wall ◽  
Rat Aorta ◽  
No Production ◽  
Paramagnetic Resonance ◽  
Physiological Importance

Nitric oxide (NO) has been shown to be the endothelium-derived relaxing factor (EDRF), and its impairment contributes to a variety of cardiovascular disorders. Recently, it has been recognized that nitrite can be an important source of NO; however, questions remain regarding the activity and mechanisms of nitrite bioactivation in vessels and its physiological importance. Therefore, we investigated the effects of nitrite on in vivo hemodynamics in rats and in vitro vasorelaxation in isolated rat aorta under aerobic conditions. Studies were performed to determine the mechanisms by which nitrite is converted to NO. In anesthetized rats, nitrite dose dependently decreased both systolic and diastolic blood pressure with a threshold dose of 10 μM. Similarly, nitrite (10 μM-2 mM) caused vasorelaxation of aortic rings, and NO was shown to be the intermediate factor responsible for this activity. With the use of electrochemical as well as electron paramagnetic resonance (EPR) spectroscopy techniques NO generation was measured from isolated aortic vessels following nitrite treatment. Reduction of nitrite to NO was blocked by heating the vessel, suggesting that an enzymatic process is involved. Organ chamber experiments demonstrated that aortic relaxation induced by nitrite could be blocked by both hemoglobin and soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). In addition, both electrochemical and EPR spin-trapping measurements showed that ODQ inhibits nitrite-mediated NO production. These findings thus suggest that nitrite can be a precursor of EDRF and that sGC or other heme proteins inhibited by ODQ catalyze the reduction of nitrite to NO.

Nitric oxide regulation of the central aortae of the toad Bufo marinus occurs independently of the endothelium

2002 ◽  
Vol 205 (19) ◽  
pp. 3093-3100 ◽  
Author(s):  
Brad R. S. Broughton ◽  
John A. Donald
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylyl Cyclase ◽  
Rat Aorta ◽  
Bufo Marinus ◽  
Organ Bath ◽  
Perivascular Nerves ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Toad Bufo

SUMMARY Nitric oxide (NO) signalling pathways were examined in the lateral aortae and dorsal aorta of the cane toad Bufo marinus. NADPH diaphorase histochemistry and nitric oxide synthase (NOS) immunohistochemistry found no evidence for endothelial NOS in the endothelium of toad aortae, but it could be readily demonstrated in rat aorta that was used as a control. Immunohistochemistry using a specific neural NOS antibody showed the presence of neural NOS immunoreactivity in the perivascular nerves of the aortae. The anatomical data was supported by in vitro organ bath physiology,which demonstrated that the vasodilation mediated by applied acetylcholine(10-5 mol l-1) was not dependent on the presence of the vascular endothelium; however, it was significantly reduced in the presence of a neural NOS inhibitor, vinyl-L-NIO (10-4 mol l-1). In addition, atropine (10-6 mol l-1) (a muscarinic receptor inhibitor), L-NNA (10-4 mol l-1) (a NOS inhibitor) and ODQ (10-5 mol l-1) (an inhibitor of soluble guanylyl cyclase) abolished the vasodilatory effect of applied acetylcholine. In conclusion, we propose that an endothelial NO system is absent in toad aortae and that NO generated by neural NOS in perivascular nerves mediates vasodilation.

Study of in vivo and in vitro resting vasodilator nitric oxide tone in normotensive and genetically hypertensive rats

1996 ◽  
Vol 310 (2-3) ◽  
pp. 175-183 ◽  
Author(s):  
José Gil-Longo ◽  
Dolores Fdez-Grandal ◽  
Marta Álvarez ◽  
Manuela Sieira ◽  
Francisco Orallo
Keyword(s):  
Nitric Oxide ◽  
Hypertensive Rats ◽  
Genetically Hypertensive Rats ◽  
Genetically Hypertensive

scholarly journals Radical Scavenger Capacity of Jabuticaba Fruit (Myrciaria cauliflora) and Its Biological Effects in Hypertensive Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Camila Gabriela de Souza ◽  
Daniela Medeiros Lobo de Andrade ◽  
Juliana Bahia Reis Jordão ◽  
Renato Ivan de Ávila ◽  
Leonardo Luiz Borges ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
High Efficiency ◽  
Biological Effects ◽  
Radical Scavenging ◽  
Differential Pulse ◽  
Radical Scavenger ◽  
Hydroxyl Groups ◽  
Hypertensive Rats

Jabuticaba is an exotic fruit native to Brazil that has been arousing medicinal interest. Using chemical (HPLC-PDA, resonance mass spectra, and NMR), electroanalytical (differential pulse voltammetry, radical scavenging assay), and pharmacological (in vivo and in vitro) approaches, we have identified its bioactive compounds and hypotensive effects on hypertensive rats. The hydroalcoholic extract of jabuticaba (HEJ) presents a great quantity of phenolic compounds, and several molecules with hydroxyl groups present high efficiency as an antioxidant. The treatment with HEJ (100 and 300 mg/kg/day, for four weeks) presented hypotensive effects on L-NAME-induced hypertensive rats, possibly improving the nitric oxide bioavailability because of its high antioxidant potential. Furthermore, renal and cardiac hypertrophies were also attenuated after the HEJ treatment. Moreover, the vascular responses to contractile and dilating agonists were improved with the HEJ treatment, which is also able to induce nitric oxide production in endothelial cells.

Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation

2005 ◽  
Vol 289 (2) ◽  
pp. G291-G299 ◽  
Author(s):  
Akiko Terauchi ◽  
Daisuke Kobayashi ◽  
Hiroshi Mashimo
Keyword(s):  
Nitric Oxide ◽  
Interstitial Cells Of Cajal ◽  
Electrical Field Stimulation ◽  
Interstitial Cells ◽  
Organ Bath ◽  
Wild Type ◽  
Basal Tone ◽  
Cells Of Cajal

Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c-Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient (nNOS−/−), eNOS-deficient (eNOS−/−), and W/Wv mice (lacking certain c-Kit-expressing ICC) with or without l-arginine or Nω-nitro-l-arginine methyl ester (l-NAME) treatment. Moreover, the basal tone and response to electrical field stimulation (EFS) were studied in organ bath using wild-type and mutant IAS. In vivo, the basal tone of eNOS−/− was higher and W/Wv was lower than wild-type and nNOS−/− mice. l-Arginine administered rectally, but not intravenously, decreased the basal tone in wild-type, nNOS−/−, and W/Wv mice. However, neither l-arginine nor l-NAME affected basal tone in eNOS−/− mice. In vitro, l-arginine decreased basal tone in wild-type and nNOS−/− IAS but not in eNOS−/− or wild-type IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS−/−, and W/Wv mice but absent in all nNOS−/− mice. EFS-induced IAS relaxation was also reduced in nNOS−/− IAS. Thus the basal IAS tone is largely controlled by eNOS in the mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be essential for the RAIR.

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